Exploring the Role of Testosterone as a Novel Anti-Nociceptive Agent in Women with Chronic Pain and Opioid Use

项目总结 有大量证据表明，女性和男性体验痛苦的方式并不相同。与男人相比，女人 在大多数临床疼痛情况下都有过多的表现，而且对 实验性疼痛。同样，在女性中使用止痛剂的情况是男性的两倍。 与之相当的严重性。女性的血清睾酮浓度不仅比女性低20倍 但男性的睾丸激素水平也会随着年龄的增长而下降。综合来看，这些数据表明 睾丸激素具有抗伤害性，这可能解释了为什么女性的发病率较高 与男性相比，慢性疼痛的严重程度。此外，服用阿片类止痛药的患者 慢性疼痛经历睾酮水平的进一步下降，因为阿片类药物有效地抑制了性腺轴。 长期服用阿片类药物的绝经前和绝经后女性的睾酮水平均下降了50% 与不使用阿片类药物的女性相比。近年来，长效阿片类药物在管理中的使用 随着许多女性服用多种阿片类镇痛剂，慢性非癌症疼痛的风险有所增加。的发展。 阿片类药物引起的性腺功能减退使这些女性丧失了睾丸激素的抗伤害性。 导致恶性循环，导致持续的慢性疼痛，尽管服用阿片类药物，使患者 长期需要更高剂量的阿片类药物。睾丸素替代治疗男性慢性阻塞性肺疾病的先前试验 阿片类药物诱导的性腺功能低下症在临床和实验疼痛方面都有所改善， 改善生活质量(QOL)。然而，尽管慢性疼痛的负担要高得多， 睾酮替代疗法对女性痛觉和耐受性的影响尚未得到研究。 这项建议的总体目标是评估生理性睾酮替代治疗的疗效。 一项改善绝经后临床和实验疼痛的双盲随机对照试验 患有慢性背痛的女性，正在接受阿片类止痛药治疗至少6个月，并且 睾丸激素。我们还将评估睾丸素替代治疗对生活质量、情绪和身体的影响。 功能。我们提出了一项为期12周的双盲、随机对照、概念验证试验来确定 每周肌肉注射生理性睾酮替代疗法与安慰剂注射的疗效比较 适用于60岁及以上患有慢性背痛和睾丸素缺乏的女性。以下是结果 将测量：1)临床疼痛，2)定量感觉测试的实验性疼痛，以及3)生活质量，情绪 和身体机能。因为慢性疼痛是一个主要的公共卫生问题，现有的治疗方法 如果这项试验证实了睾丸激素治疗的好处，患者将 有一种廉价、相对安全和易于管理的药物，有可能 转变对这些患者的护理。

PROJECT SUMMARY There is abundant evidence that women and men do not experience pain equally. Compared to men, women are overrepresented in the majority of clinical pain conditions and also exhibit greater sensitivity to experimental pain. Similarly, use of analgesics is twice as common in women, compared to men, for conditions of comparable severities. Women not only have 20-fold lower serum testosterone concentrations compared to men but also experience a reduction in testosterone levels with age. Taken together, these data suggest that testosterone has anti-nociceptive properties which may explain why women have a higher incidence and severity of chronic pain compared to men. Additionally, patients who are prescribed opioid-analgesics for chronic pain experience further reduction in testosterone levels as opioids potently suppress the gonadal axis. Both pre- and postmenopausal women on chronic opioids demonstrate >50% reduction in testosterone levels compared to women not using opioids. In recent years, the use of sustained-action opioids in the management of chronic non-cancer pain has grown with many women taking multiple opioid analgesics. The development of opioid-induced hypogonadism deprives these women of the anti-nociceptive properties of testosterone and leads to a vicious cycle resulting in perpetuation of chronic pain despite being on opioids, subjecting patients to long-term requirement of even higher doses of opiates. Previous trials of testosterone replacement in men with opioid-induced hypogonadism have shown improvement in both clinical and experimental pain, and improvement in quality of life (QOL). However, despite having significantly higher burden of chronic pain, the efficacy of testosterone replacement on pain perception and tolerance has not been studied in women. The overall goal of this proposal is to evaluate the efficacy of physiologic testosterone replacement in improving clinical and experimental pain in a double-blind, randomized-controlled trial in postmenopausal women with chronic back pain who are being treated with opioid-analgesics for at least 6 months and have low testosterone. We will also assess the efficacy of testosterone replacement on QOL, mood and physical function. We propose a 12-week double-blind, randomized-controlled, proof-of-concept trial to determine the efficacy of physiologic testosterone replacement with weekly intramuscular injections versus placebo injections in women age 60 years and older with chronic back pain and testosterone deficiency. The following outcomes will be measured: 1) clinical pain, 2) experimental pain with quantitative sensory testing, and 3) QOL, mood and physical function. Because chronic pain is a major public health problem for which existing therapies are suboptimal and only provide partial relief, if this trial confirms benefits of testosterone therapy, patients will have an inexpensive, relatively safe and easy to administer medication available that has the potential to transform the care of these patients.